Hereditary ataxia with onset in adulthood
Gene: TMEM106BThe rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 4:49 p.m. | Last Modified: 9 Mar 2022, 4:49 p.m.
Panel Version: 2.141
Comment on list classification: This gene has been flagged for review at the next GMS panel update (added 'for-review tag) as there is only enough evidence for TMEM106B to be rated AMBER on this panel.
Only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this could be reviewed if evidence emerges of a more prominent ataxic phenotype.Created: 12 Nov 2020, 5:21 p.m. | Last Modified: 12 Nov 2020, 5:21 p.m.
Panel Version: 2.16
Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.
Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).
Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with only mild cerebellar atrophy identified in one patient on brain MRI.Created: 12 Nov 2020, 5:19 p.m. | Last Modified: 12 Nov 2020, 5:19 p.m.
Panel Version: 2.15
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Leukodystrophy, hypomyelinating, 16 OMIM:617964
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 15 Apr 2019, 10:21 a.m.
Multiple cases reported in the two papers all associated with a single recurrent de novo variant c.754G>A p.(Asp252Asn)Created: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hypomyelinating leukodystrophy 16, 617964
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Publications for gene: TMEM106B were set to
Tag for-review was removed from gene: TMEM106B.
Source Expert Review Amber was added to TMEM106B. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Phenotypes for gene: TMEM106B were changed from Leukodystrophy, hypomyelinating, 16 OMIM:617964 to Leukodystrophy, hypomyelinating, 16, OMIM:617964; Leukodystrophy, hypomyelinating, 16, MONDO:0054791
Gene: tmem106b has been classified as Green List (High Evidence).
Tag missense tag was added to gene: TMEM106B. Tag for-review tag was added to gene: TMEM106B.
Phenotypes for gene: TMEM106B were changed from Hypomyelinating leukodystrophy 16, 617964 to Leukodystrophy, hypomyelinating, 16 OMIM:617964
Mode of inheritance for gene: TMEM106B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene: TMEM106B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: tmem106b has been classified as Green List (High Evidence).
Added phenotypes Hypomyelinating leukodystrophy 16, 617964 for gene: TMEM106B
Source NHS GMS was added to TMEM106B.
gene: TMEM106B was added gene: TMEM106B was added to Hereditary ataxia - adult onset. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: TMEM106B was set to